The present invention relates to optically active compounds which are useful as starting materials for physiological active materials, functional materials and the like, and as intermediates. However, as the compounds have optical isomers, and in practical uses, it is necessary to use only one of these antipodes. Further, when racemates or compounds having low optical purity are used, the obtained compounds apparently do not develop enough physiological activity or functionality.
In order to obtain an optically active substance, it is necessary to conduct an asymmetric synthesis, to optically resolve a recemate (itself typically obtained by a synthetic chemical technique), or to convert from an optically active starting material by a stereochemical synthetic method. In many cases, the process is troublesome and disadvantageous industrially, and scarce materials should be used.
Accordingly, it is desired to develop a technique for obtaining optically active compounds by an industrially advantageous method.
As ester of 3-hydroxypentanoic acid, methyl 3-hydroxypentanate and ethyl 3-hydroxypentanate are known. Both of them have low optical purity and the operation process is troublesome. Even if the process can be used experimentally, it is unable to use the process industrially.
For example, G. Frater reported a method in which ethyl R-3-hydroxypentanate is obtained by asymmetric reduction of ethyl 3-ketopentanate with baker's yeast. The method has the following disadvantages (G. Frater, Helv. Chim. Acta, 62, 2829(1979)). ##STR2##
(1) The product has low optical purity and can not be used as a physiological substance or a starting material of a functional compound. According to our determination, the purity is about 40% ee.
(2) Since the concentration of substrate is low in a reaction system, a large scale of reaction equipments is reguired for mass-producing. For example, 250 g of baker's yeast, 375 g of glucose and 2.5 liters of water are required in the reaction of 25 g of substrate.
(3) As a large volume of baker's yeast and water are contained in a system, it takes long time for removing the baker's yeast and for extracting the objective from water.
(4) Generally, in the case of asymmetric reduction with baker's yeast, the product has different optical purity in each reaction process.
(5) Only one of antipodes is obtained. In this case, only one R-compound is obtained.
Therefore, Mori et al tried asymmetric reduction of substrate containing S atoms in the molecule, which is able to become equivalent in organic chemical convertion, with high temperature yeast (pichia terricola) to obtain an optically purified hydroxy ester (Enzyme Function and Precision Organic Synthesis, published by C. M. C., pp 60-61 (1984). In this case, there are industrially troublesome disadvantages as follows. ##STR3##
(1) As described above, yeast is used in this process, so that the concentration of substrate is very low and the production process is very complicate.
(2) The preparation of starting substrate is difficult, and methyl 3-hydroxypentanate should be again obtained after the asymmetric reduction. Accordingly, the process can not be industrially utilized.
(3) The method provides only one of the antipodes.
Furthermore, Hasegawa et al obtained methyl R-3-hydroxypentanate from pentanic acid by oxidation reaction in the presence of Candida rugosa. However, there are the following disadvantages (J. Hasegawa et al, J. Ferment. Technol., 61, 37 (1983)). ##STR4##
(1) The obtained product has a low optical purity of 83-93% ee. For obtaining a substance having high optical purity, the material is led to the ester of 3,5-dinitro benzoic acid, and then a preferential crystallization method which is primitive and inefficient should be used.
(2) As described above, the concentration of the substrate is very low and the operation of purification is very troublesome.
(3) The method provides only one of antipodes.
Firstly, the conventional methods as described above can not provide a substance having high purity. Otherwise, the substance is obtained through complex processes. Secondly, as the concentration of the substrate in the reaction system is low and the operation of purification is extremely troublesome, the methods are unsuitable for the production of an industry level. Thirdly, only one of antipodes can not be obtained, and different methods must be studied for obtaining the other antipode. All of the above reports do not refer to substrates of esters having long alkyl chains and to their effect.